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Chrysin Reduces Heart Endoplasmic Reticulum Stress-induced Apoptosis by Inhibiting PERK and Caspase 3-7 in High-fat Diet-fed Rats

Overview
Journal Mol Biol Rep
Specialty Molecular Biology
Date 2024 May 25
PMID 38796673
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Abstract

Background: Chrysin (Chy) is a naturally occurring flavonoid found in fruits, vegetables, honey, propolis, and many plant extracts that has shown notable medicinal value. Chy exhibits diverse pharmacological properties, including anti-oxidative, anti-inflammatory, anti-apoptotic, anti-cholesteremic, and cardioprotective. However, the influence of Chy in mitigating high-fat diet (HFD)-induced ER stress of rat myocardium remains unknown.

Purpose: The current work intended to determine the therapeutic potential of Chy against HFD-induced endoplasmic stress-mediated apoptosis.

Methods: To evaluate the therapeutic value of Chy in HFD-induced endoplasmic stress-mediated apoptosis in the myocardium; The male wistar rats were divided into different groups; control, HFD control, HFD fed followed by Chy-treated and HFD fed followed by atorvastatin (Atv) treated rats.

Results: When compared to the control group, the HFD-fed rats had significantly higher levels of marker enzymes such as CK-NAC and ALP, as well as lipid peroxidation and lipid profile (TC, TG, LDL, and VLDL). Chy therapy greatly reversed these marker enzymes and the lipid profile. qRT-PCR Studies showed that Chy supplementation considerably improved Nrf2 and its target genes. In addition, Chy lowered the expression of PERK, CHOP, ATF6, GRP78, and Caspase-3 genes in the heart tissue of HFD-fed rats. Immunohistochemistry results demonstrated that Chy substantially enhanced the Nrf2 and reduced PERK and Caspase3-7 protein expression in HFD-fed rats.

Conclusion: The current study concluded that Chy may mediate the cardioprotective effect by activating Nrf2 and inhibiting PERK signaling pathway against ER stress-mediated apoptosis induced by HFD. Therefore, supplementation with Chy could serve as a promising therapeutic target against HFD-induced ER stress-mediated cardiac complication.

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